Compliant Blood Vessel Graft

ABSTRACT

A graft includes a flexible, resilient, generally tubular external support and a blood vessel segment, carried within and having an ablumenal surface in contact with and supported by the tubular support, the graft being capable of resilient radial expansion in a manner mimicking the radial compliance properties of an artery.

CROSS REFERENCE

This application is a divisional of U.S. Non-Provisional patentapplication Ser. No. 10/987,313, filed on Nov. 12, 2004 and entitled“Compliant Blood Vessel Graft”, which is a continuation-in-part of U.S.Non-Provisional patent application Ser. No. 10/834,360, filed on Apr.28, 2004 and entitled “Compliant Venous Graft” which application claimspriority to U.S. Provisional Application Ser. No. 60/466,226 titled“Compliant Venous Stent” filed on Apr. 28, 2003, the contents of whichbeing incorporated herein in their entirety.

FIELD OF THE INVENTION

This invention involves a graft involving a blood vessel segment and asupportive sheath chosen to provide the graft with mechanical complianceproperties which resemble those of a healthy native artery.

BACKGROUND OF THE INVENTION

Various types of vascular prostheses are known or available.Commercially available synthetic vascular grafts in use are commonlymade from expanded polytetrafluoroethylene (e-PTFE), or woven, knitted,or velour design polyethylene terephthalate (PET) or Dacron®. Theseprosthetic vascular grafts may have various drawbacks. When used forrepairing or replacing smaller diameter arteries, these grafts may faildue to occlusion by thrombosis or kinking, or due to an anastomotic orneointimal hyperplasia (exuberant cell growth at the interface betweenartery and graft). Another problem may involve expansion and contractionmismatches between the host artery and the synthetic vascularprosthesis, which may result in anastomotic rupture, stimulatedexuberant cell responses, and disturbed flow patterns and increasedstresses leading to graft failure.

Problems also exist with the use of autologous saphenous vein grafts inthese applications. Use of autologous saphenous vein grafts to bypassblockages in coronary arteries has become a well-established procedure.However, their success in the long term has been limited. In thecoronary position, the literature reports a low (45-63%) patency of veingrafts after 10-12 years. It is believed that these failures result fromremodeling of the implanted vein in response to greatly increasedinternal pressure, that is, as the vein is required to function as anartery. In general, arteries have substantial musculature and, althoughable to expand diametrically in response to increased internal pressure,are capable of withstanding normal arterial pressure variances. Veins,on the other hand, are not required to withstand arterial pressurevariances and are relatively incapable of withstanding the higherarterial pressures without substantial bulging. In this regard, thenominal venous diameter seen under nominal venous pressure is seen toapproximately double upon exposure to arterial pressure.

Increases in lumenal diameter of these magnitudes in vein segmentimplants are accompanied by increases in tangential stress. Tangentialstress has been shown to be proportional to the lumenal radius-wallthickness ratio. In healthy arteries, this ratio remains constant acrossmultiple species. However, this does not occur in veins. It is believedthat a vein's smooth muscle cells increase their growth rate and secreteextra-cellular matrix components in response to such increases intangential stress. This becomes a remodeling response, and is likely anattempt by the vein to reduce the lumenal radius-wall thickness ratio,and consequently the tangential stress. However, it appears that thesereactions overcompensate in the veins, resulting in the phenomenon ofneointimal hyperplasia yielding grossly thickened and stiff graft walls.As the dilation of the vein segment continues, the resulting mismatchbetween the vein and artery diameters may lead to disturbance of flowpatterns, which may also favor the formation of thrombi.

Problems also exist when tubular prostheses are used as exteriorlyaccessible shunts to facilitate access to the circulatory system for,e.g., the administration of medicines and nourishment and for dialysisprocedures.

SUMMARY OF THE INVENTION

It has now been found that a blood vessel segment such as a veinsegment, if externally supported by an appropriate, flexible,radially-resiliently tubular support, can provide a valuable tubularprosthesis. A vein segment so supported can function in much the samefashion as the artery that is to be replaced. That is, it functionswithout undue bulging or aggravated mismatching phenomena leading tograft failure. Unless otherwise indicated, the term “compliance” meansthe ratio of the diameter change of a vessel as it expands in the radialdirection in response to a given change in vessel pressure, and thevalues for compliance referred to below result from dynamic, in vitrotesting. As described in greater detail below, the compliance of venousgraft is largely dependent upon the compliance of the external, radiallyresilient support.

The invention in one embodiment, accordingly, relates to a flexible,resilient, generally tubular external support within which may besupported a blood vessel segment such as a vein segment to form a graft.The tubular support is capable of resilient radial expansion in a mannermimicking the compliance properties of an artery, and compliance figuresin the range of 3 to 30%/100 mm Hg are appropriate. The tubular supportmay be formed of a knitted or woven fiber mesh that is so formed as toexhibit the needed compliance properties.

The invention in certain embodiments provides a venous graft forreplacement of a section of an artery. The graft comprises a flexible,resilient, generally tubular external support and a vein segment carriedwithin and having an ablumenal surface in contact with and supported bythe tubular support, the venous graft being capable of resilient radialexpansion in a manner mimicking the compliance properties of an artery.Compliance figures in the range of 3 to 30%/100 mm Hg are appropriate,although compliance values ranging up to 50%/100 mm Hg may be desired insome instances. The tubular support may take the form of a fiber mesh,such as a knitted, braided or woven mesh, the fibers of which may, ifdesired, be appropriately crimped to provide the required resiliency andcompliance.

In other embodiments, the invention relates to a method for producing avenous graft for use, for example, in replacing a section of an artery.A segment of a vessel is provided, and is sheathed in a generallytubular support in supportive contact with the ablumenal surface of thevein segment. The support is sufficiently flexible and radiallyresilient as to provide the resulting graft with compliance propertiesmimicking the compliance properties of the artery to be replaced.Sheathing of the vessel segment within the tubular support may beaccomplished by supporting the generally tubular support upon anexterior surface of an applicator having an internal passage withinwhich is positioned the vessel segment, and removing the applicator topermit the tubular support to come into supportive contact with theablumenal surface of the vessel segment. Axial dimensional changes inthe tubular support may be controlled as necessary to provide the graftwith the desired compliance properties mimicking arterial complianceproperties.

Other embodiments of the invention relate to vessel grafts that includea flexible, resilient, generally tubular external support formed of ashape memory alloy, and a vessel segment carried within and having anablumenal surface in contact with and supported by the tubular support.The shape memory support may be placed around a vessel segment when theshape memory material is in a first enlarged configuration. The tubularsupport comes into supportive contact with the ablumenal surface of thevessel when the support is transformed, as by a temperature increase orupon removal of an introducer tube over which the tubular support issupported, into a second configuration different from the firstconfiguration. The shape memory support in its second configuration mayexhibit superelastic properties and in any event is sufficientlyflexible and resilient as to provide the venous graft with complianceproperties mimicking the compliance properties of, for example, anartery. Compliance figures in the range of 3 to 30%/100 mm Hg areappropriate. The tubular support may take the form of a wire mesh madeof shape memory alloy, such as a knitted or woven mesh, the wires ofwhich may, if desired, be appropriately crimped to provide the requiredresiliency and compliance.

The invention is described hereafter primarily with respect to graftsthat utilize veins that are received within a tubular support and thatcan function as replacements for arterial segments in, for example,coronary by-pass procedures, but the grafts of the invention may alsoutilize other vessels such as arteries, including treated vein andartery segments from donor animals such as vessels of porcine and bovineorigin.

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1 is a pressure versus diameter graph typifying the characteristicsof a native vein, native artery, a non-compliant stented vein, and acompliant stented vein;

FIG. 2 is a schematic cross-sectional view of an artery;

FIG. 3 is a representative pressure versus strain graph;

FIG. 4 is a pressure versus graft diameter graph;

FIG. 5 is a photograph of a tubular support in a first configuration,shown in an axially compressed and radially expanded configuration andsupported on a plastic tube;

FIG. 6 is a photograph of the tubular support of FIG. 5 in an axiallyelongated and radially reduced configuration to conform to a vein outerdiameter;

FIG. 7 is a side view of the graft of FIG. 6, showing a length-governingelement;

FIG. 8 is a schematic view of braided elements;

FIG. 9 is a perspective view of a braided tubular support;

FIG. 10 is a schematic view of knitted elements;

FIG. 11 is a side view of a section of a knitted tubular support;

FIG. 12 is a view of angular pre-braiding crimped elements;

FIG. 13 is a perspective, schematic view of an angular pre-braidingcrimped tubular support;

FIG. 14 is a view of rounded pre-braiding crimped elements;

FIG. 15 is a view of angular pre-knitting crimped elements;

FIG. 16 is a view of rounded pre-knitting crimped elements;

FIG. 17 is a broken-away, perspective view of a post-braiding crimpedtubular support;

FIG. 18 is a broken-away, perspective view of a venous graft showing aportion with anti-fraying element;

FIG. 19 is a broken-away, perspective view of one embodiment utilizingan applicator for assembling a venous graft;

FIG. 20 is a broken-away, perspective view of the use of a modifiedapplicator for assembling a venous graft;

FIG. 21 is a photographic, perspective view of a section of a knittubular support;

FIG. 22A is a schematic cross-sectional view of an assembly device;

FIG. 22B is a schematic, prospective view of a step in the assembly of avessel graft;

FIG. 23 is a schematic, prospective view of another step in the assemblyof a vessel graft;

FIG. 24 is a schematic cross-section of an attachment of a vessel to atubular support;

FIG. 25 is a schematic cross-section of another attachment of a vesselto a tubular support;

FIG. 26 is a schematic cross-section of yet another attachment of avessel to a tubular support;

FIG. 27 is a schematic cross-section of the attachment of a vessel to atubular support utilizing a sleeve;

FIG. 28 is a schematic cross-section of the attachment of a vessel to atubular support utilizing an adhesive tape;

FIG. 29A is a cross section of a clip bearing an adhesive tape segment;

FIGS. 29B through D are schematic views showing stages in theapplication of an adhesive tape segment to a vessel graft;

FIG. 30 is a schematic view showing severance on a bias of the vesselgraft also shown in FIG. 29D;

FIG. 31 is a schematic view of the attachment to an artery of a segmentshown in FIG. 30; and

FIG. 32 is a photograph of a portion of a bioprosthetic access vesselgraft.

DETAILED DESCRIPTION OF THE PRESENTLY PREFERRED EMBODIMENTS

Applicants have recognized that significant deficiencies attend to thepast methodologies and devices relating to the increased pressuresexperienced by vein grafts utilized in arterial positions. The increasedpressures lead to excessive dilation of vein grafts in arterialcirculation, leading to the development of intimal hyperplasia, whichcauses occlusion of the vessel.

Intimal hyperplasia is believed to be a primary reason for vein graftfailure. In this context it is known that intact endothelium acts in amanner to protect against the proliferation of underlying vascularsmooth muscle cells, known as VSMC. The intact endothelium also plays arole in VSMC contractile responses. The VSMC have also been shown torelease factors with long term physiological effects on the endothelialcells, including maintenance of a non-proliferative state. Bycomparison, the pathogenesis of intimal hyperplasia in a vein graft mayfollow the sequence of dilatation under arterial pressure;overstretching to maximum capacity; disruption of borders of endothelialcells; rupture of internal elastic membranes; migration of smooth musclecells into the intimal layer and resultant unbalanced proliferation;atrophy of media and further consolidation of stiffness; and graftarteriosclerosis with traumatic media necrosis and atrophy, as well aspathological surface and wall stress and strain. These phenomena mayresult in a decrease in vein graft patency within six years. Intimalhyperplasia may be observed in such grafts from about 16 months, whileanastomotic intimal hyperplasia may occur at about 18 months, andarteriosclerosis may occur from about 45 months.

Others have attempted to overcome certain of these problems by use ofmetallic or polymeric external structures designed to arrest thedilation of the vein graft. FIG. 1 graphs blood pressure against vesseldiameter, with D₀ representing the vessel diameter at zero pressure. Asshown in this graph, lines 16, 18 represent the normal diastolic, i.e.low (80 mm Hg) and normal systolic, i.e. high (120 mm Hg) physiologicalblood pressure range for humans. Line 21 may represent the diameter ofan artery (D_(A)) at 100 mmHg, and line 23 may represent the diameter ofa vein (D_(V)) at the same pressure of 100 mmHg. An unstented nativeartery reacts to pressure loading as shown at line 32, and an unstentedvein reacts to the same loading as shown at line 35. The use of knownstents with vein grafts results in movement of line 35 in the directionshown by arrow 38, resulting in the approximate profile indicated atline 42 showing the response of a pressure loaded vein and non-compliantstent combination. Although this prevents over-dilation, and someadvantage accrues, this may lead to further unhealthy sequelae. Also, tothe extent that vein-stent combination devices may be shown to limitsome of the dilation and intimal hyperplasia in the mid-graft region,they may not be able to prevent intimal hyperplasia at the anastomoses.This can be a significant problem for vein grafts that are transplantedinto the arterial circulation vasculature. Prior attempts to resolvethese problems fail to recognize the full implications of a vein beingused in these situations. Accordingly, factors in the design of avein-graft that may have a significant impact on its long term patencymay have been missed.

One important factor in proper remodeling is that of proper cyclicstretch. Applicants are able to incorporate this concept into vein-stentgrafts of the invention. In similar manner, the role of vascularendothelial growth factor (VEGF) in vascular smooth muscle cells may bevery important to the design of a preferred arterial vein-stent graft.It is known that low concentrations of VEGF may play a role inpreserving and repairing the arterial lumenal endothelial layer.Further, it is suggested that activation of the VEGF receptor KDR isaffected by cyclic stretch. Applicants believe that the phenomenon ofupregulation of VEGF expression by physiological stretching of vascularsmooth muscle cells is one reason for redesigning a vein-stent graftwhich has improved, controllable cyclic stretch features.

A further consideration is the influence of tensile stress/strain on thestructure and organization of smooth muscle cells during development andremodeling, particularly as to the orientation of such cells. In alarger topographical sense, this may also relate to the role of bloodflow in the formation of focal intimal hyperplasia in known vein grafts,including inducement of eddy blood flow at locations of graft-hostdiameter mismatch.

These considerations and deficiencies can be addressed with the variousstructures and methodologies of the present invention in which a veingraft is provided that exhibits compliance properties mimicking those ofhealthy arteries. Radial expansion and contraction of the graft ispermitted in a manner that mimics the radial expansion and contractionof an artery to at least closely approach the desired result in whichthe vein graft, its connections to adjacent arterial ends or stumps, andthe adjacent arterial portions tend to expand and contract in a similarmanner, to thereby substantially avoid anastomotic compliancemismatches. This is accomplished through the use of a flexible,resilient, generally tubular external support that engages the ablumenalsurface of a vein segment carried within the support, the support beingso fabricated as to functionally provide the graft with the complianceproperties of an artery.

Compliance Properties

As noted earlier, compliance is the ratio of the diameter change of avessel in the radial direction to a given change in vessel pressure, andthe values for compliance referred to below result from dynamic, invitro testing. Compliance values are reported here as percentage changesin the internal diameter of a vessel per a 100 mm Hg change in vesselpressure, as measured in the range of normal blood pressures, that is,from about 80 mm Hg to about 120 mm Hg. In the laboratory, it isconvenient to measure compliance through the use of an elongated balloonstructure over which a candidate tubular support is positioned.Distilled water at about 37° C. is pumped into the balloon to cause itto inflate, and the pressure within the balloon is cycled between 0 mmHg and 140 mm Hg at a frequency of about 72 cycles per minute to mimic anormal pulsatile blood flow. The change in internal volume is measuredbetween 0 mm Hg and 140 mm Hg to provide pressure/volume data. From thisdata is subtracted the pressure/volume data resulting from repeating theprocedure with the balloon alone, and from the resulting pressure/volumedata the percentage change in the internal diameter of the tubularsupport between 80 and 120 mm Hg can be calculated. It is convenient toexpress this radial compliance value as %/100 mm Hg.

The compliance of an implanted venous graft may be measured in vivothrough the use of ultrasound techniques in which the vein graft isvisualized in a cross-sectional view and the dimensional change of thevessel with varying blood pressure is recorded for at least one andusually a number of cardiac cycles. The cross-sectional lumenal area ofthe vein graft is measured for the smallest cross-sectionalconfiguration and the largest cross-sectional configuration for onecardiac cycle. The smallest cross-sectional configuration of the veingraft lumen is associated with diastolic blood pressure whereas thelargest cross-sectional configuration is associated with systolicpressure. The cross-sectional lumenal area values for diastolic andsystolic blood pressure are used to calculate the lumenal diametervalues and the vein graft compliance. Compliance values of a venousgraft measured in vivo often are slightly larger that the compliancevalues measured in the laboratory, and the compliance values referred toherein are laboratory values resulting from the in vitro measurementsdescribed above.

FIG. 2 is a sectional representation of vascular tissue useful forillustrating the relation of the natural arterial structure with theprosthetic venous graft structure of the invention. The naturaladventitial layer 95 of an artery 98 is comprised of two main tissuetypes that contribute to the mechanical properties of the naturalartery, namely elastin and collagen. The mechanical properties of thesetwo soft tissue components are described in Table I below:

TABLE I Soft Tissue Elastic Modulus (Pa) Max Strain (%) Elastin 4 × 10⁵130 Collagen 1 × 10⁹ 2-4

As shown in the above table, these two soft tissue types have largedifferences in mechanical properties. Elastin is very elastic, andcollagen is very stiff in comparison. These two tissue types arecombined in the adventitial layer to produce a non-linear elasticresponse. As shown in FIG. 3, the combined effect of the characteristicsof elastin 101 and collagen 104 (having a greater role at higherstrains) results in a non-linear response curve (shown loading at 135and un-loading at 137) within the physiological pressure range of anatural artery between about 80-120 mm Hg. This characteristic ofpulsatile expansion and contraction of arteries requires fine mechanicalcompliance of any prosthetic graft, i.e., a close mimicking by theprosthetic device of the mechanics and timing of the natural arterydistending and reshaping under change in blood pressure.

From an engineering standpoint, the following relationships may behelpful from a design standpoint in producing venous stent grafts of theinvention.

$C_{d} = {\frac{\Delta \; D}{D_{diastolic}\Delta \; P} \times 100 \times 100\mspace{14mu} {mmHg}}$

in which C_(d) is compliance, P is blood pressure, ΔP is the differencebetween systolic and diastolic blood pressures, D is vessel diameter,and ΔD represents the diameter change between systolic and diastolicpressures.

The stiffness of blood vessels is stated as a stiffness index (β), andis a measure of the changes of curvature and diameter, stated as:

$\beta = {\frac{\ln \frac{P_{systolic}}{P_{diastolic}}}{\frac{\Delta \; D}{D_{diastolic}}} = {D_{diastolic}\frac{{\ln \; P_{systolic}} - {\ln \; P_{diastolic}}}{\Delta \; D}}}$

A related characteristic of blood vessels is that of elastic modulus(K), which is considered a measure of stiffness, and is stated as:

$K = {\frac{V_{diastolic}\Delta \; P}{\Delta \; V} \propto \frac{D_{diastolic}\Delta \; P}{\Delta \; D} \propto \frac{1}{C}}$

in which C is compliance, V_(diastolic) is the vessel volume per unitlength at diastole, and ΔV is the difference in unit volumes betweensystole and diastole. In terms of diametric compliance, as an example,

$K = {{D_{diastolic}\frac{P_{systolic} - \; P_{diastolic}}{D_{systolic} - D_{diastolic}}} = {D_{diasolic}\frac{\Delta \;}{\Delta \; D}}}$

FIG. 4 shows that the Elastic Modulus (K), as defined in the aboveequations, is proportional to the secant S₁ of the pressure-diametercurve PD₁, plotted on a linear scale (left y-axis in FIG. 4), betweendiastolic and systolic pressure. The slope,(P_(syst)−P_(diast))/(D_(syst)−D_(diast)), of the secant S₁ is a goodapproximation to the slope of the pressure-diameter curve PD₁ in thatpressure range. From the above equations for the Elastic Modulus (K) itcan be appreciated that the Elastic Modulus (K) is not equal to theslope of the secant S₁ but is proportional to the slope by a factorD_(diastolic). Compliance (C_(d)) is approximately proportional to theElastic Modulus (K) hence it is approximately proportional to theinverse of the secant S₁ of the pressure-diameter curve PD₁ betweendiastolic and systolic blood pressure.

The stiffness index (β) is proportional to the secant S₂ of thepressure-diameter curve PD₂ between diastolic and systolic bloodpressure when the pressure-diameter curve is plotted on a logarithmicpressure scale (right y-axis in FIG. 4). The slope of the secant S₂ is(ln P_(syst)−ln P_(diast))/(D_(syst)−D_(diast)) and is a goodapproximation to the slope of the pressure-diameter curve PD₂ in thatpressure range. It can be again appreciated, from the above equationsfor the Stiffness Index (β) that the Stiffness Index (β) is not equal tothe slope of the secant S₂ but is proportional to the slope by a factorD_(diastolic).

Compliance data of natural human vessels is categorized by vessel typeand by age of the vessel (i.e., age of patient). For example, a commoncarotid artery has about a 6.6%/100 mm Hg compliance value. The valuesfor a superficial femoral artery and a femoral artery are 6-10%/100 mmHg. A value for a saphenous vein, however, is about 4.4%/100 mm Hg,while an aorta ranges generally from about 20-50%/100 mm Hg, dependingon the location. Also, the lengths of grafts according to location inthe body must be considered, and substantial lengthwise variance ingraft lengths is not uncommon. It is also known that the diameter ofvarious arteries change over time, and this may have a significantimpact on overall compliance values. Returning to FIG. 1, line 80represents the pressure-diameter data that certain embodiments of venousgrafts of the invention seek to emulate, wherein the complianceproperties of a native artery (line 32) is closely mimicked.

Support Materials and Manufacture

The radially resilient support may be manufactured from any biologicallyacceptable material that possesses the ability to be shaped into atubular structure having the required compliance. Polymeric fibers maybe employed, such as polyurethanes, polyethylene terephthalate,polypropylene, and polytetraflouroethylene, and good results may beobtained through the use of wires of such metals as stainless steel andcobalt-chromium alloys. Wires made of shape memory alloys such asnitinol may be used to advantage. Shape memory elements or filaments maybe made of one or more shape memory materials as exemplified in thefollowing table, it being understood that this is not to be consideredan exhaustive list. Also, any metal or metal alloy may be coated with apolymer for improved biocompatibility, recognizing that the polymer mayor may not be biodegradable.

ALLOYS POLYMERS Ag—Cd Two component system based onoligo(Σ-caprolactone)dimethacrylate and N-butyl acrylate Au—CdPolyurethanes Cu—Al—Ni Polynorborenes Cu—Sn Poly(ether ester)sconsisting of poly(ethylene oxide) and poly(ethylene terephthalate)(EOET copolymers) Cu—Zn Ethylene vinyl acetate copolymers Cu—Zn—SiPolystyrene polybutadiene copolymer Cu—Zn—Sn Cu—Zn—Al In—Ti Ni—Al Ni—TiFe—Pt Mn—Cu Fe—Mn—Si

With respect to shape memory alloys, other design considerations includetemperatures, different diameters and radial compliance, shapetransformation dimensional changes, and wire thicknesses. Generally,shape memory alloys and shape memory polymers may have transformationtemperatures which are below physiological temperatures, i.e., 37° C.,to ensure self-righting responses. Preferably, transformationtemperatures will also be above room temperature to ensure that theshape memory material reinforcing does not need to be refrigerated forstorage purposes. Thus, the ideal shape memory transformationtemperatures will likely be between 21° and 37° C. This transition mayeither be a two-way or a one-way directional transition, with acurrently preferred embodiment including a two-way directionaltransition. The transition temperature range can either be a short, i.e.0.5° C., or a long transition temperature range, i.e. 10° C., where theshape is proportionally regained over this temperature range. Forexample, for a desired temperature transition to be 100% complete at 25°C. but with it starting at 20° C., then this would yield a temperaturerange of 5° C. The changes in radial diameter due to the shape memorymaterial experiencing transformation dimensional changes is preferablyin a range of from 5% to 30%.

An embodiment of a tubular support utilizing a shape memory alloy isillustrated in FIGS. 5 and 6. FIG. 5 shows an arterial reinforcementtubular support 77 formed of one or more shape memory material elements165. These elements are braided, but may also be knitted or woven, intoa generally tubular structure designed for placement around a portion ofa vein to produce an arterial graft. In this example, a shape memoryalloy is employed because of its so-called “superelastic” propertiesrather than its ability to undergo temperature-induced phase changes,although some phase change from austenite to stress-induced martensitemay occur. In FIG. 5, the braided tube is positioned on a hollow plasticstraw as representing a vein segment, and has been compressed axially toproduce an increase in diameter. By extending the braided tube axially,as shown in FIG. 6, the tube becomes reduced in diameter to providesupport to the vein segment.

The shape memory braided material shown in FIGS. 5 and 6, if used alsofor its phase transformation properties, may be supplied in a firstconfiguration (which may be in the martensite phase) which can be easilymanipulated to receive a vein segment 86 within the structure, and asecond configuration (shown in FIG. 6, which may be in the highertemperature austenite phase) which has a “remembered” narrower diameterconfiguration to provide support to the vein segment. The contact ofinner surfaces 170 of the structure with ablumenal surfaces 175 of thevein segment 86 is shown also in FIG. 7. The resilience of shape memorymaterials can be controlled by altering compositions, temperingprocedures, wire diameters, etc., so that a tubular support fashionedfrom this material may mimic (when combined with the minimal mechanicalvalues of a vein segment) the compliance values of a host artery inorder to optimize the venous graft-artery interaction. This aspect ofcompliance mimicking has components of expansion, recoil, timing, andtissue remodeling. In this example, the vein-stent compliance values arechosen to closely mimic those of a healthy native artery. Whereas theshape memory wires are shown as braided in FIGS. 5, 6 and 7, they mayalso be knit, and in fact the knit configuration appears to offercertain advantages.

Radially resilient tubular supports may be knit from metal wire, such asstainless steel and cobalt-chromium alloys. Metal wires ranging indiameter from about 25 to 150 micrometers are appropriate for knitsupports with diameters in the range of 35 to 50 micrometers beingparticularly useful, although larger or smaller diameters may beemployed as desired. For braided tubular supports, metal wires rangingin diameter from about 37 to about 170 micrometers are appropriate,although larger or smaller diameters may be employed.

Knitting procedures may be performed by known methods using, forexample, a LX96 knitting machine manufactured by the Lamb KnittingMachine Corporation. Favorable radial compliance and tubular dimensionalproperties may result from knitting the tubular structure in a mannerproviding loops that alternate in the circumferential direction betweenlarger and smaller loops, as shown in FIG. 21. In this Figure, smallerloops 250 are shown alternating circumferentially with larger loops 251.Such alternating loop sizes typically present themselves visually aslongitudinal stripes extending axially along the tubular support, as theadjacent loops of each size align in the longitudinal axis. Each closedend of the loop may be either rounded or generally square-shaped orvariations in between, and, the sides of the loop may turn outward, beparallel, or turn inward. The latter design has shown some advantage inacting like a spring and assisting in the stability of the overalldimensions of the tubular structure, and maintaining its compliancecharacteristics.

The knitted or braided tubular support may then be subjected to crimpingto provide crimps extending, for example, about the circumference of thetubular support (that is, in the manner shown in FIG. 17). One way ofdoing this is through the use of an axially fluted mandrel that isinserted into the tube and is pressed outwardly against a wall of thetube to force the wall against a complementary shaped outer female moldto bend the knitted or braided wires and to form a circumferentialcrimp, the crimp resulting from each flute or raised ridge of themandrel extending axially of the support.

A compliant venous graft using various metals or polymers for thetubular support may be provided in several ways. Embodiments may beadvantageously provided in knitted form. FIGS. 8 and 9 show material 165in a braided configuration, and FIGS. 10 and 11 show material 165 in aknitted configuration. Mechanical characteristics of the tubular supportmay be enabled by the type of shaping and relational structures formedon the elements making up the knit or braided structures. It iscontemplated that a technique involving crimping of the material 165 toachieve angular crimps (shown in FIGS. 12 and 13), formed prior to thebraid or knit construction, and rounded crimps (shown in FIG. 14) mayprovide acceptable results. Crimping techniques that may be appropriatewith pre-knit configurations are shown in FIG. 15 (angular crimps) andFIG. 16 (rounded crimps). Another technique for achieving certainperformance characteristics of braided or knitted shape memory materials165 is to perform crimping after braiding or knitting, i.e.post-braiding or post-knitting. FIG. 17 shows one embodiment of material165 formed in a braided configuration and having a post-braided crimpingoperation applied to form a crowned pattern to achieve desired crimpcharacteristics.

Crimp angle and pitch density may be important variables in certainembodiments of the current design of the tubular supports. It isunderstood, however, that certain advantages of this invention may stillbe achieved without use of crimping. Ranges of crimp angle arepreferably from about 10° to 85° to the line of lay of the reinforcingwire or braid. The crimp size may vary from 0.01 to 5 mm in length. Itis desired that the braid or helical wires have a pitch angle that mayvary from about 5-85° to the axial length of the vein graft.

Applicants have identified certain crimping techniques that relate tocrimping either before or after braiding or knitting. For example, inpost-braid crimping the material braids are produced according toexisting techniques, after which macroscopic longitudinal crimping isimparted to the tubular mesh using a post-braid crimping tool. However,according to the material and specific configuration of the stent, ifthe post-braid crimping of braided tubes does not achieve sufficientcompliance then alternate methods are possible. One example is to effectpre-braid crimping, thereby setting the memory of a shape memorymaterial in a crimped configuration and subsequently straightening thematerial before braiding. The crimp is thus induced upon exposure tophysiological temperatures.

In certain embodiments, it is appropriate to provide for “jump” grafts,or “skip” grafts to communicate a stented graft with another vessel. Toaccommodate such grafts, an opening is made in the resilient, externaltubular support of a compliant graft of the invention so that a portionof the vessel wall itself is exposed through the opening to enable ajump graft to be attached at that location. It is desirable to providefor such openings in the support wall prior to assembly of the compliantgraft. When the tubular support is made of a shape memory alloy, such asnitinol, an opening in the mesh may be made by supporting the mesh on anappropriately shaped mandrel and gently moving the fibers forming themesh away from what is to be the center of the opening. A pin or othersupport is placed in the opening to keep it open, the pin being held andsupported by the mandrel. The tubular support, constrained in thisshape, is subjected to a heat treatment, e.g., in the 500° C. range, fora short period of time and then cooled. The resulting tubular support,in its austenite phase, exhibits the usual super elasticity associatedwith nitinol and other shape memory alloys, and the opening thusprovided in the wall of the tubular support remains open and accessiblefor formation of a jump graft. By selection of an appropriately shapedand sized tubular support with a pre-formed access opening, a surgeonmay produce a graft prosthesis having an opening in the wall of thetubular support positioned where desired for formation of a jump graft.

The external tubular support adjusts the mechanical and geometricalproperties of the vein graft to match or mimic healthy arterialproperties and therefore adapt to the arterial pressure of the hostartery. Accordingly, this results in substantial matching of the lumenof the vein graft and the host artery, the substantial matching ofcompliance of the vein graft and the host artery, and substantialmatching of the radius to wall thickness ratio (r/wt) of the vein graftto the host artery. As noted above, optimization of the vein-stentcompliance should ensure that the vein-stent graft mimics the behaviorof arteries regarding the non-linear stiffening with increasing diameterdue to elevated blood pressure, “locking” at a maximum pressure, andthen demonstrating dynamic recoil in a timely manner.

When venous grafts utilizing knit or braided tubular supports are cut atangles suitable for end-to-end anastomoses, either at generally rightangles or in scallop-like shape, the ends of the supports may experiencefraying (see, for example, FIG. 17). Certain methods and structure arehelpful to eliminate such fraying. In one embodiment, adjustable rings210 of bioabsorbable or biodegradable material are placed generallycircumferentially around a portion of the material 165, and in contactwith external surfaces 217, as shown in FIG. 18. The number of rings maybe varied as needed. The location of the rings may be adjusted to theposition of anastomoses where vein and tubular support need to be cut.The cut or suture may be carried out through the ring, and the ring maybe absorbed or degraded over a predetermined time, as desired.

Another embodiment of a structure to prevent fraying of a knit orbraided tubular support when it is cut is the use of polymer coating forthe fiber mesh. This feature may also provide the benefit of preventinggluing of joints and contact zones of elements of the stent. However,use of the radially compliant tubular support as a reinforcing structuremay advantageously involve bonding of the ablumenal surface of a veinsegment to confronting internal surfaces of the support. This attachmentor connection may be accomplished through the use of a glue or othermaterial having adhesive or connecting characteristics. In oneembodiment, a fibrin glue or other material having adhesive orconnective characteristics may be sprayed on designated portions of thevein (as exemplified at 283 in FIG. 20) and/or the tubular support.Another embodiment includes placement of a material on designatedportions of the lumenal surfaces of the tubular support so as to providethe characteristics of contact adhesion and/or bonding when theseportions contact the vein. However, the glue or other material must notinhibit the function of the tubular support. It is desirable that thecontact of the tubular support with the ablumenal vein segment surfacebe reasonably uniform along the length of the support, and that regionsof much higher force of the support against the ablumenal wall of thevein be avoided.

Performing the anastomoses of small-diameter unsupported vein grafts inthe coronary position is complicated by the tendency of the free end ofthe vein to collapse on itself, thereby obscuring the lumen and makingit difficult for the surgeon to identify a suitable position for theplacement of sutures. The application of an external tubular support(referred to sometimes herein as a stent) on a vein graft potentiallyfurther complicates the suturing, as the collapsed vein is situatedinside (and at least partially obscured by) the non-collapsed stentmaterial. By attachment of the ablumenal surface of the vein to thelumenal surface of the stent, however, the stent offers support to thevein to prevent it from collapsing, and this is particularly the casewhen stents formed from shape memory alloys are employed. As notedabove, adjustable rings 210 and various adhesives may be employed tobond the confronting surfaces of the vessel and the supporting tubularstructure together.

Attachment of the vessel surface to the tubular support stent can beachieved in various ways. In one embodiment, a covering gel is employedthat attaches to the vessel wall and surrounds and entraps the stentwires, thereby attaching the stent to the vessel, this embodiment beingschematically depicted in FIG. 24, the tubular support fibers beingshown at 320, the vessel wall at 322 and the gel at 324. Examples ofsuch gels are synthetic gels (such as modified polyethylene glycol,polyvinyl alcohol, acrylic gels, etc) and biological gels (such asfibrin, gelatin, and albumin glues). In another embodiment shownschematically in FIG. 25, an adhesive glue 326 such as a cyanoacrylateattaches the stent to the vessel ablumenal wall, the glue adhering toboth the vessel and the stent.

In another embodiment, shown schematically in FIG. 26, individual fibers320 of the stent are coated with an adhesive material 328 containinggroups reactive to the vessel tissue. This material may be eitherdirectly applied on the metal wires (FIG. 26) or on a polymeric coatingwith which the wires are pre-coated. This material coating, appliedoptionally over a polymer coating on the wires, may also be employed inother embodiments, for example, those shown in FIGS. 24, 25, 27 and 28.

In a preferred embodiment, a sleeve is placed over the assembled stentedvessel. As schematically depicted in FIG. 27, the sleeve 330 mayprimarily offer mechanical support for the stent to prevent fraying ofcut edges, in the manner discussed above in connection with FIG. 18,while having minimal if any effect on the mechanical properties of theassembly, such as compliance. Referring to FIG. 28, a sleeve maycomprise an adhesive tape 332 having an elastic backing material 334bearing an adhesive material 336 having a consistency enabling it topenetrate between fibers of the tubular mesh and adhesively contact theablumenal surface of the vessel. The adhesive may have the consistencyof a gel. The elastic material may be a fabric, and may be formed from avariety of materials that are inherently elastic (e.g. polyurethaneelastomers) or materials that are not elastic by themselves, but may actin an elastic fashion due to the fact that they are coated with orentrapped in an elastic gel-like material that constitutes the adhesiveportion of the tape. Crimped fibers made from polyesters (PET) ordegradable materials such polylactic acid (PLA) or polyglycolic acid(PGA) or copolymers thereof may also be used for the elastic material.

The adhesive material 336 should be of sufficient cohesive strength andadhesive strength to the vessel wall by virtue of mechanicalinterlocking and/or covalent chemical binding to attach the stent to thevessel during normal handling during implantation. As the vessel tissuecontains both nucleophilic (amino, thiol and hydroxyl groups) andelectrophilic (carboxyl) groups, the adhesive may employ a number ofchemical groups capable of reacting with the vessel wall. Aldehydes,acyl chlorides, activated esters, isocyanates or carboxylic acids (plusactivators such as carbodiimides) are examples of compounds capable ofreacting with nucleophilic groups on the tissue, and alcohols and aminesmay be employed to react with the electrophilic carboxylic acid groupson the tissue (in the presence of an activator, e.g. a carbodiimide).

In general, the adhesive may be composed of synthetic polymers, in theirswollen or un-swollen states. Gel-like characteristics may be impartedby the adhesive material itself, or by swelling the material with asolvent or a plasticizing agent, such as water. Gels offer theadvantages of having viscoelastic properties that may simulate themechanics of vessels to some extent, and of being capable of deformingto facilitate contact and binding of the gel to the tissue through thegaps in the stents. In addition, gels may contribute to the strength ofthe bond between the vessel wall and the stent by mechanicalinterlocking. Adhesives may be non-degradable cross-linked materialssuch as polyethylene glycols, polyimines, polyacrylates (e.g.,polyacrylic acid, polyacrylamides, poly(hydroxyethyl methacrylate), andco-polyacrylates. Degradable and/or resorbable adhesives may includemultifunctional polyethylene glycols containing degradable end groupsand/or crosslinked with degradable crosslinkers, and non-crosslinked orlightly crosslinked polyvinyl alcohol.

As noted above, the adhesive material desirably is functionalized withgroups capable of reacting with the vessel tissue. For example, anadhesive may comprise crosslinked polyacrylic acid gels functionalizedwith aldehyde groups (e.g., via a diamine bridge) capable of reactionwith tissue amines. As another example, a polyvinyl alcohol, the degreeof hydrolysis, molecular mass and tacticity (and thus crystallinity)have been adjusted to render the adhesive slowly dissolvable in vivo canbe appropriately functionalized with groups reactive toward tissuegroups.

Although the adhesive tape 332 may be applied as desired to the stentedvessel, a preferred method involving particular stented vessels having asupportive tubular structure derived from a shape memory materialutilizes a pre-assembled clip comprising a disposable elastic metal clipand a segment of the adhesive tape, as schematically depicted in FIGS.29 A through D. Referring to FIG. 29A, the metal clip 340 is shaped toprovide an opening for reception of the stented vessel, and may, forexample, be generally “C” shaped. The clip contains within it a sectionof the adhesive tape 332, the adhesive surface 336 facing the interiorof the clip and the elastic backing adjacent the inside surface of theclip. As desired, the assembled clip may be positioned within the jawsof a pliers-like applicator 342 (FIG. 29B). In use, a section 344 of astented vessel is inserted into the opening of the clip as shown in FIG.29B. The jaws of the applicator 342 are closed on each other, thestented vessel becoming temporarily flattened as shown in FIG. 29C andthe adhesive penetrating between fibers of the stent to adhesivelycontact the ablumenal surface of the vessel. The jaws of the applicatorare opened, enabling the section of the stented vessel to resume itssubstantially circular cross-sectional configuration. The metal clip isremoved, and excess tape is removed from the edges to provide thestented tube structure schematically shown in FIG. 29D.

An alternative method involves the employment of a tape dispenser thatcontains a continuous roll of the tape, sections of the tape beingsevered from the roll and applied to the stented vessel by hand.

The application of the tape to the stented vessel can be performed at aposition required by the surgeon according to the implant position. FIG.30 shows how a taped section 350 of a stented vessel may be cut toprovide a biased opening that may be sutured to, for example, a coronaryartery. The taped section is cut so that the resulting open end isconfigured to conform generally to the ablumenal surface of an artery orother vessel to which the stented vessel is to be attached. FIG. 30shows a cut being made generally along the dashed lines to providesegments 352, 354. FIG. 31 shows how the bias-cut taped end of thesegment 352 may be sutured to a length of artery 356, and it will beunderstood that the artery has a surgically prepared, axially extendingslit (not shown) providing an opening through its wall about which thesegment 352 is sutured to communicate the graft with the artery.

By appropriately cutting the taped portion, the end of the segment canbe shaped to conform as needed to the external contour of variousvessels to which it is to be attached. For example, a graft may beshaped to make an appropriately angled (e.g., 45 degrees) juncture witha coronary artery, the artery and the stented graft segment lyinggenerally in the same plane. In another example, the stented graft maycross over a vessel to which it is to be attached. In this “cross-overjump” configuration, slit-like openings are provided in the tapedsection of the graft segment and the vessel, and the taped section andthe vessel are sutured together about their confronting openings and toestablish fluid communication through the openings. The slit-likeopenings may be made such that they are approximately parallel as theyconfront each other. In yet another example, the stented graft and avessel may be positioned substantially parallel and in contact with eachother. In this “longitudinal jump” configuration, slit-like, desirablyaxially extending openings are made in the taped section of the stentedgraft and in the vessel, and suturing is performed as above.

Applicants have further recognized the need for a device to facilitateassembly of the radially compliant tubular support and a vein segment.It is desirable that such an applicator should not obscure the stentlumen, and that it should allow for easy insertion of the vein. It isfurther recognized that a design whereby diameter is increased by lengthcompression, as in a braided configuration, would allow easy slipping ofthe tubular support over a vein. FIG. 19 illustrates this concept incombination with an applicator 279 to apply the braided support 284 to avein 86. This longitudinal braid contraction phenomena (shown earlier inFIGS. 5 and 6), and which must be carefully managed at the time ofjoining the vein to the stent, is likely quite useful to achieving thegoals of an applicator 279, as noted above. This applicator may alsofacilitate placement of anti-fraying rings 210. In one embodiment, themethod of using the applicator comprises the steps of: providing themeans of longitudinally contracting a stent; holding the stent in thecontracted position with increased stent diameter resulting; inserting avein into the stent lumen; and distending the stent longitudinally whilethe vein is inserted simultaneously until the stent is slipped over thedesired portion of the vein. Further design considerations must ensurethat the stent will not be fixed to the vein in a longitudinallyover-distended or contracted state, so as to ensure that thepredetermined mechanical stent properties remain viable.

FIG. 20 shows an embodiment in which a tubular support 185 is receivedalong the outer surface of an applicator 281 having an internal passage,and, while passing the vein segment 86 from within the applicatorpassage, the tubular support is drawn onto the ablumenal surface of thevein segment. The applicator here may be a thin walled tube resembling asoda straw.

FIGS. 22A and B show the end of a syringe 300 having a mechanism 302 forengaging and immobilizing the end of a blood vessel and the surroundingtubular support. The mechanism may be any mechanism adapted to connectto the ends of open tubes, and one such mechanism may include an outertubular portion 301 within which is received an end portion 304 of ablood vessel, the mechanism including an axially movable internaltapered mandrel 305 that is inserted in the vessel. Axial movement ofthe mandrel (to the left in FIG. 22) pinches and captures the end of theblood vessel between the mandrel and an introducer sheath carrying atubular support, the sheath and tubular support together being shown inFIG. 22A as 303.

Referring to FIGS. 22B and 23, in one assembly method, the distal end304 of the vessel is supported by the mechanism 302 with the proximalend of the vessel being attached to a cord 306. The tubular support 308(FIG. 23) is carried exteriorly of and is supported by an introducertube 310. A plug 312 sized to engage the interior wall of the introducertube is attached to the proximal end of the vessel. The introducer tube310, bearing on its outer surface the tubular support 308, is drawn overthe cord 306, the plug and the vessel segment, the cord being maintainedunder tension to facilitate sliding the introducer tube over the vessel.The end of the tubular support is gripped by the mechanism 302 (FIG.22A). Thereafter, the introducer tube is withdrawn proximally away fromthe mechanism 302. By frictionally engaging the interior surface of theintroducer tube, the plug 312 exerts a gentle longitudinal tension onthe proximal end of the vessel, causing the vessel to shrink somewhat indiameter. As the introducer tube is withdrawn, the tubular support 308comes into contact with the ablumenal surface of the vessel. Once theintroducer tube has been completely withdrawn, the gentle longitudinaltension on the vessel is relaxed and the vessel itself seeks to returnto its original larger diameter to thereby more closely contact thetubular support.

The plug may be made of any appropriate material that frictionallyengages the interior wall of the introducer tube as it is withdrawn, anda soft urethane rubber plug, for example, may be employed.

Although assembly of the stented graft has been described as occurringaway from the vein or artery to which it will eventually becomeattached, in practice, such assembly can be affected by attaching oneend of the harvested vessel segment to the artery or vein with a cordattached to its other end. The mesh tubular support is then urged gentlyover the ablumenal surface of the vessel while maintaining gentletension on the cord until the support is positioned where desired.

It is desired that the support be applied to a vein at a predeterminedlength which is associated with a particular desired compliance. Alength-defining support feature or system should ensure a predeterminedsupport length. This is particularly true with respect to braidedsupports, and perhaps less important with knit supports in which radialresilience is less dependent upon the amount to which the support isextended axially.

In a braided support, and to a much lesser extend in a knit support,compliance and related mechanical properties are linked to the supportlength through the pitch angle. Imparting a change in length results ina change in pitch angle and compliance. However, the compliance of thesupport is a mandatory characteristic which is optimized, as notedabove, to mimic the compliance of a normal healthy host artery. Whenapplying a support to a vein segment, it is important to accuratelyaccommodate the predetermined tubular support length, even afterlongitudinal contraction of the support for the attachment of thesupport to the vein.

With braided, and to a much lesser extent knit supports, axial supportlength may be controlled, for example, through the use of an axiallyextending, relatively inextensible element, (as for example the thread78 in FIG. 7), that restrains the tubular support from unwanted axialextension. The thread may be woven through the support mesh and may befastened, as by welding, to the various wires that the thread encountersalong the length of the support so that as the support is stretchedaxially, the extent of axial elongation is controlled by the thread asthe thread is drawn taut. Moreover, this feature may enable a length ofthe tubular support to be divided into portions of appropriate length,with the permitted axial extension of each portion controlled by thesection of thread within it. As presently envisioned, a vein segment maybe sheathed in a tubular support as discussed in detail above, with theintent of cutting out a smaller segment of the resulting venous graftfor use in the surgical replacement of an artery, and the venous graftthat is thus used will have vein and tubular support ends that arecoextensive.

Various generally tubular external wire mesh supports were fabricatedfrom metal wires by braiding and by knitting, some being crimped andothers not, and the diametrical compliance of each was measured usingthe in vitro diametrical compliance testing outlined above. The measuredcompliance values were dependent upon many variables, including wiresize, tightness of braid or knit, etc. The following values wereobtained:

Compliance %/ Design 100 mmHg A Braided Non-crimped 0.9 B BraidedCrimped 5.6 C Braided Crimped 1.8 D Knitted Non-crimped 3.4 E KnittedCrimped 7.9 F Knitted Crimped 8.0 G Knitted Non-crimped 10-21 H KnittedNon-crimped  9-21 I Knitted Non-crimped   16->30 J KnittedNon-crimped >30     K Knitted Non-crimped 10-16 L Knitted Non-crimped21-29 M Knitted Non-crimped 22-28 N Knitted Non-crimped >30     OKnitted Non-crimped 10-15 P Knitted Non-crimped  9-11 Q KnittedNon-crimped 13-24 R Knitted Non-crimped >30    

A surgical procedure is proposed for use of the graft disclosed herein.This procedure, which may also be viewed as a simple method forplacement of a venous reinforcement structure, includes, in thisexample, application of the compliant external tubular support duringthe procedure of vein excision. In many instances, vein excision isconsidered a standard part of a surgical operation, which is usuallydone by an assistant at a time when the surgeon is still in thepreparatory phase of the operation. When an autologous blood vessel suchas a segment of the saphenous vein is harvested for use in accordancewith the invention, it may contain side branches that need to be removedbefore the vein is enclosed within the tubular support. Closure of theopening that remains after removal of a side branch can be accomplishedin several ways. Surgically placed sutures or small clips such as Ligaclips may be used to ligate small sections of branches. However, when abranch has been removed flush with the ablumenal surface of the vessel,it is desirable to close the resulting opening in the vessel by suturingto reduce interference with the tubular support. Purse string suturesare appropriate. To avoid undue narrowing of the lumen of the vesselwhen a purse string suture is pulled tight, the ends of the purse stringsuture are preferably tightened by pulling them in the longitudinaldirection, i.e., axially of the vessel, rather than in a directiontransverse to the longitudinal direction of the vein.

In one embodiment, an initial step includes dissection and freeing of asaphenous vein. The saphenous vein is dissected free in a standard way,leaving it in situ while ligating and cutting off its branches asdiscussed above. The second step involves testing for potential wallleaks of the vein. In order to test the isolated saphenous vein forpotential leaks, it is normally cannulated distally and cold heparinisedblood is injected while the proximal end is occluded. This inflation ofthe vein (using old techniques) with a syringe creates pressures of upto 350 mm of Hg and is often a main reason for traumatic damage of thevein wall. Therefore, a pressure limiting mechanism may be positionedbetween the vein cannula and the syringe. The external tubular supportcannot be applied yet because leaks in the vein wall need to be freelyaccessible for repair. Therefore, no over-distention protection isplaced around the vein yet, necessitating the limitation of theinflation pressure to a level suitable for detecting any leaks ofconcern but less than a level deemed to cause unacceptable damage, suchas, for example, in one embodiment, 15 mm of Hg, the pre-maximaldilatation pressure for veins. The tissue remodeling functions ofapplicants' invention become more critical in view of the importance ofleak testing and the reality of possible damage to the intimal layer inthe vein during even the most carefully performed leak testing.

The next step involves assembling the harvested vein segment and anexternal tubular support of this invention. In this step, the tubularsupport (typified here as a knit support) is mounted on a tube orstraw-like applicator within which is positioned the vein segment. SeeFIG. 20. The straw is then removed axially, leaving the support and veinin contact to form the venous graft. Over-extension of the tubularsupport is prevented using a length-limiting central thread or othermeans, as described above. As required, the vein segment is theninflated under arterial blood pressures of 120 mm of Hg, causing it tocontact the tubular support inner lumenal surfaces. In certainembodiments, an adhesive securing the tubular support to the vein willensure that the vein does not collapse during the surgical procedurewhen no internal pressure is applied. Again, it should be recognized(without limitation) that this is one of several ways to accomplish theabove objectives.

The following sequence may occur at this or another time during theprocedure. One of the external anti-fraying rings or cuffs is slid tothe end of the vein, and a typical double-S-cutting line is used toprepare the end for the first anastomoses. The thin cuff preventsfraying of the tubular support and also gives the vein tissue andtubular support a uniformity which makes the surgical process ofstitching the vein to the host artery in an end-to-side fashion mucheasier. Another thin anti-fraying ring is then slid down from theapplicator to a position where either a side-to-side anastomoses for asequential graft is being performed, or where the vein is being cut atan appropriate graft length. The half of the sliding cuff which remainson the original vein will make the process of the anastomoses to theproximal host artery much easier. In the case of a coronary arterybypass graft, for example, the end of the remaining vein protected bythe other half of the cuff is used for the next distal graftanastomoses.

Although the invention has been described primarily in connection withthe use of autologous blood vessels to form a stented graft as areplacement for diseased vessels, the invention has other uses as well.External stent structures can be used to allow repeated access to thevascular system for administration of medicines or nourishment or theadministration of dialysis procedures. Exterior access grafts may besubject to frequent penetration by hypodermic needles, and it isdesirable not only that the vessel walls of the graft retain theircapacity to be punctured many times, but also that the wounds thusformed in the vessel wall self-seal to a large extent.

In accordance with the invention, an external stent structure 360 asshown in FIG. 32 may be produced from a blood vessel segment harvestedfrom human or non-human animals, such as segments of bovine or porcinearteries, the vessels having been treated, as by known aldehyde fixingor decellularization. A flexible, resilient tubular support of the typedescribed herein may be placed over the resulting venous or arterialvessel segment to provide a bioprosthetic access graft to enable readyaccess to the cardiovascular system. For this purpose, one may form abioprosthetic device utilizing a suitably treated bovine or porcineartery or vein segment by placing the segment within an elastic,resilient tubular support sized to contact and squeeze against theablumenal surface of the vessel when the vessel is filled with blood, aswhen it is being used as a shunt between an artery and a vein of apatient. In this manner, once a hypodermic needle has been inserted andwithdrawn from the wall of the vessel, the elastic, resilient tubularsupport tends to exert a squeezing force on the vessel, forcing theedges of the wound to close upon one another.

FIG. 32 is a photograph showing an access graft formed from adecellularized porcine artery segment 362 contained within a knitted,resilient tubular support 364. This figure illustrates a puncture wound366 formed by a syringe 368. The edges of the wound are brought togetherby the squeezing action imparted by the knitted support. It may be notedthat the knitted support, or braided support if desired, may be madewith loops or openings 370 that are sized to receive a hypodermic needleof the desired diameter. For hypodermic needles commonly used fordialysis procedures, for example, needle sizes, and hence the size ofopenings between fibers of the tubular support, may be in the range ofabout 1.8 and 2.1 mm.

As structures have become increasingly complex, not only in design butalso in the range of material use, pure analytical methods have begun tofail in describing the behavior of such structures. Due to thescientific challenge of closely matching a vascular graft of the typedescribed herein to a host, analytical methods are rendered somewhatobsolete. Development of a prosthetic vascular graft which mimics themechanical requirements and dynamic compliance of a normal healthyartery is made possible, however, with certain old tools, particularlycut and try methods in which incremental changes are made to thematerial or structure of the tubular support to modify its complianceproperties, and the resulting properties are used to guide furtherchanges. Empirical data or constitutive equations and mathematicalanalyses may be used for certain features. Alternatively, the use ofnumerical modeling with such tools as, for example, Finite ElementModels and Methods, relying on continuum mechanics, along with certainother tools makes this level of customization feasible.

While the embodiments of the invention described herein are presentlypreferred, various modifications and improvements can be made withoutdeparting from the spirit and scope of the invention. The scope of theinvention is indicated by the appended claims, and all changes that fallwithin the meaning and range of equivalents are intended to be embraced

1. A blood vessel graft comprising a flexible, fiber mesh configured asa generally tubular external support and a blood vessel segment carriedwithin and having an ablumenal surface in contact with and supported bythe tubular support, the support having resilient radial expansion andcontraction characteristics contributing to the compliance properties ofthe graft.
 2. The graft of claim 1 including an adhesive adhering thetubular support to the ablumenal surface of the vessel to resistcollapse of the vessel within the support.
 3. The graft of claim 1including an adhesive tape positioned around a portion of the tubularsupport, the tape including an adhesive that extends through the fibermesh support and into adhesive contact with the ablumenal surface of thevessel.
 4. The graft of claim 2 wherein said adhesive at least partiallyembeds said fiber mesh and adhesively contacts the ablumenal surface ofthe vessel.
 5. The graft of claim 2 wherein said adhesive is formed as acoating on the fibers of the fiber mesh.
 6. A graft for replacement of asection of an artery, the graft comprising a flexible, resilient, knitwire mesh configured as a generally tubular external support and a bloodvessel segment carried within and having an ablumenal surface in contactwith and supported by the tubular support, the support having resilientradial expansion and contraction characteristics that provide the graftwith compliance properties mimicking those of an artery.